Phase III Randomized Trial of Stereotactic Ablative Radiotherapy (SAbR) for Oligometastatic Advanced Renal Carcinoma (SOAR)
Overview
- Phase
- Phase 3
- Intervention
- Computed Tomography
- Conditions
- Metastatic Renal Cell Carcinoma
- Sponsor
- ECOG-ACRIN Cancer Research Group
- Enrollment
- 472
- Locations
- 216
- Primary Endpoint
- Overall survival (OS)
- Status
- Active, not recruiting
- Last Updated
- 29 days ago
Overview
Brief Summary
This phase III trial compares the effect of stero-ablative radiotherapy (SAbR) followed by standard of care systemic therapy, to standard of care systemic therapy alone, in patients with kidney cancer that has spread from where it first started (primary site) to a limited (2-5) number of places in the body (metastatic). Study doctors want to find out if this approach is better or worse than the usual approach for metastatic kidney cancer. The usual approach is defined as the care most people get for metastatic kidney cancer which includes systemic therapy such as immunotherapy (given through the veins) and/or small molecular inhibitor (tablets taken by mouth). Radiotherapy uses high energy x-rays to kill cancer cells and shrink tumors. SAbR uses special equipment to position a patient and deliver radiation to tumors with high precision. Giving SAbR prior to systemic therapy may kill more tumor cells than the usual approach, which is systemic therapy alone.
Detailed Description
PRIMARY OBJECTIVES: I. To compare overall survival (OS) between patients receiving SAbR + systemic therapy (SABR+ST) versus systemic therapy (ST) only. II. To compare average adverse event (AE) score between SAbR+ST arm and ST only arm. SECONDARY OBJECTIVES: I. To compare global health status / quality of life (QOL) between patients receiving SAbR+ST versus ST only. II. To compare progression-free survival (PFS) between the arms. EXPLORATORY OBJECTIVES: I. To estimate PFS on first line systemic therapy (PFS-SST) in the SAbR+ST arm and compare with first line systemic therapy PFS of the ST arm. II. To explore local control from SAbR by looking at the amount of local failures after SAbR in the SAbR+ST arm. III. To assess the cost-effectiveness between the arms in terms of cost per unit gain in quality-of-life years. QOL OBJECTIVES: I. To compare global health status / quality of life (QOL) between patients receiving SabR+ST versus ST only using the National Comprehensive Cancer Network (NCCN) / Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index -19 item (NFKSI-19). II. To compare quality-adjusted survival between patients randomized to receive SabR+ST vs ST alone using European Quality of Life (EUROQOL) 5-dimension, 5-level (EQ-5D-5L) at 3, 6, 9, 12, 18, and 24 months. III. To compare global health status / QOL of the NFKSI-19 at all of the 3, 6, 9, 12, 18, and 24 month time points between patients randomized to receive SabR+ST versus ST alone. IV. To compare scale scores of the NFKSI-19 (disease-related symptoms - physical disease-related symptoms - emotional, treatment side effects, and function \& well-being) at 3, 6, 9, 12, 18, 24 months between patients randomized to receive SabR+ST versus ST alone. V. To compare time to global quality of life deterioration between patients randomized to receive SabR+ST versus ST alone using NFKSI-19. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive standard of care systemic therapy on study. ARM II: Patients undergo repeated SAbR until progression and then receive standard of care systemic therapy on study. Patients in both arms undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient must be \>= 18 years of age
- •Patient must have a pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma (RCC) prior to randomization
- •Patient may have any RCC histology except a histology that has a sarcomatoid component
- •Patient must have primary site addressed by local therapy. If the primary RCC is intact, the patient must undergo local treatment to the primary before randomization
- •Patient must have favorable or intermediate International Metastatic RCC Database Consortium (IMDC) risk (0-2) at the time of randomization
- •Patient must have a total of between 2 and 5 metastatic lesions, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria with imaging obtained within 45 days prior to randomization
- •Patient must have a documentation from a radiation oncologist confirming that all sites are amenable to SAbR
- •Patient may have received prior therapy in the adjuvant setting as long as potential trial participants have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment
- •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- •Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
Exclusion Criteria
- •Patient must not have brain metastases
- •Patient must not have metastasis involving the following locations: ultra-central (within 2cm of carina) lung, invading gastrointestinal tract (such as esophagus, stomach, intestines, colon, rectum), skin, and scalp
- •Patient must not have received any prior systemic therapy (except for adjuvant setting) for metastatic RCC
- •Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
- •History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
- •Active tuberculosis (purified protein derivative \[PPD\] response without active TB is allowed)
- •Uncontrolled hypertension (systolic blood pressure \[BP\] \> 190mmHg or diastolic BP \> 110mmHg)
- •Major surgery within 30 days prior to randomization
- •Any serious (requiring hospital stay or long term rehab) non-healing wound, ulcer, or bone fracture within 30 days prior to randomization
- •Any arterial thrombotic (ST elevation myocardial infarction \[STEMI\], non-STEMI \[NSTEMI\], cerebrovascular accident \[CVA\], etc.) events within 180 days prior to randomization
Arms & Interventions
Arm I (usual care)
Patients receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial.
Intervention: Computed Tomography
Arm I (usual care)
Patients receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial.
Intervention: Magnetic Resonance Imaging
Arm I (usual care)
Patients receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial.
Intervention: Questionnaire Administration
Arm I (usual care)
Patients receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial.
Intervention: Systemic Therapy
Arm II (SAbR, usual care)
Patients undergo repeated SAbR until progression and then receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial.
Intervention: Computed Tomography
Arm II (SAbR, usual care)
Patients undergo repeated SAbR until progression and then receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial.
Intervention: Magnetic Resonance Imaging
Arm II (SAbR, usual care)
Patients undergo repeated SAbR until progression and then receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial.
Intervention: Questionnaire Administration
Arm II (SAbR, usual care)
Patients undergo repeated SAbR until progression and then receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial.
Intervention: Stereotactic Ablative Radiotherapy
Arm II (SAbR, usual care)
Patients undergo repeated SAbR until progression and then receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial.
Intervention: Systemic Therapy
Outcomes
Primary Outcomes
Overall survival (OS)
Time Frame: From randomization to death from any cause, assessed up to 10 years
The repeated confidence interval method will be utilized. At each scheduled interim analysis, a one-sided 95% repeated confidence interval of hazard ratio (stereotactic ablative radiotherapy \[SAbR\] + standard therapy \[ST\] / ST) will be computed, using the partial likelihood estimate, to test non-inferiority in OS for SAbR+ST arm.
Incidence of adverse events (AEs)
Time Frame: From randomization up to 6 months
All patients who receive treatment, regardless of eligibility, will be evaluated for AE/toxicity. AE score will be calculated in 3-month intervals starting from randomization. To calculate the AE score for a 3-month interval, for each patient, the AE sub-score for each Common Terminology Criteria for Adverse Events (CTCAE) categories (there are 26 AE categories listed in CTCAE version 5) will be aggregated based on the highest grade of AE experienced in each CTCAE category.
Secondary Outcomes
- Progression-free survival (PFS)(From randomization to progression of disease, assessed up to 10 years)